Androgenetic alopecia affects approximately 50% of the population by the age of 50. See Hoffmann R, Happle R., “Current understanding of androgenetic alopecia. Part II: clinical aspects and treatment,” Eur. J. Dermatol. 2000: 10 (5): 410-417. Topical minoxidil is the most common drug used for the treatment of androgenic alopecia. Although topical minoxidil exhibits a good safety profile, the efficacy in the overall population remains relatively low at 30-40%. Clinical studies have shown that following 16 weeks of minoxidil (5%) mono-therapy approximately 38.6% of patients experience hair growth. See Olsen E A, Whiting D, Bergfeld W, et al., “A multicenter, randomized, placebo-controlled, double-blind clinical trial of a novel formulation of 5% minoxidil topical foam versus placebo in the treatment of androgenetic alopecia in men,” J. Am. Acad. Dermatol. 2007: 57 (5): 767-774. To observe significant improvement in hair growth, minoxidil is typically used daily for a period of at least 3-4 months. Due to the significant time commitment and low response rate, a biomarker for predicting patient response prior to therapy would be advantageous.
The exact mechanism of action for minoxidil based treatment of androgenetic alopecia is not completely understood. However, in vitro studies have demonstrated that minoxidil sulfate is the active metabolite of minoxidil. See Buhl A E, Waldon D J, Baker C A, Johnson G A., “Minoxidil sulfate is the active metabolite that stimulates hair follicles, J. Invest. Dermatol. 1990: 95 (5): 553-577. The conversion of minoxidil to minoxidil sulfate is catalyzed by the enzyme minoxidil sulfotransferase (SULT1A1) in the hair follicle. See Baker C A, Uno H, Johnson G A., “Minoxidil sulfation in the hair follicle, Skin Pharmacol. 1994: 7(6): 335-339. Correlation between SULT1A1 expression in the scalp and minoxidil response has been reported. See Buhl A E, Baker C A, Dietz A J, Murray F T, Johnson G A, “Minoxidil sulfotransferase activity influences the efficiency of Rogaine® topical solutions (ts)—enzyme studies using scalp and platelets,” J. Invest. Dermatol. 1994: 102: 534.
While minoxidil has also been approved by the FDA for treatment of female hair loss, for most women minoxidil is only marginally successful at retaining existing hair. Some men for whom minoxidil is less effective have been successfully treated with finasteride; however, the same cannot be said of females for whom minoxidil is ineffective. Studies have thus far failed to show the effectiveness of finasteride in the treatment of female androgenetic alopecia.
There are significant differences between male androgenetic alopecia and female androgenetic alopecia. Apart from the different baldness patterns, male and female alopecia follow a different mechanism. In men, alopecia is related to the normal high androgen levels in males, combined with an underlying sensitivity of the hair roots to androgens. Women, however, have roughly 10 times lower androgen levels than men, and the absolute amount of androgen is a less significant factor than the increased sensitivity of the hair roots to androgens.
Finasteride therapies that are successful at hair re-growth and maintenance in males have failed to show significant improvement in females. Further, for minoxidil therapy to be effective it often must be used for a prolonged period of time without knowing if it is effective.
Among various individuals, whether male or female, there is a broad variability in the response of different people to various hair loss treatments. This variability is presumed to be a result of genetic factors contributing to variable enzyme activity in the follicles, making a one-size-fits-all approach difficult to achieve. It would therefore be advantageous to be able to have an effective diagnostic and treatment method where patients could be selected and treated on the basis of criteria such as enzyme activity, which would identify some people as being likely to benefit from treatment by minoxidil and other drugs, while identifying other individuals in which treatment is not likely to be effective.